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To demonstrate bioequivalence of a 2.5 mg saxagliptin/1000 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 1000 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Other | Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions |
|
| Arm B | Other | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions |
|
| Arm C | Other | Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal |
|
| Arm D | Other | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saxagliptin | Drug | Tablet, Oral, 2.5 mg, Once Daily, 1 week |
|
| Measure | Description | Time Frame |
|---|---|---|
| Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Metformin PK Parameter AUC(INF) |
| Measure | Description | Time Frame |
|---|---|---|
| BMS-510849 PK Parameter AUC(INF) | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| BMS-510849 PK Parameter AUC(0-T) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mds Pharma Services | Lincoln | Nebraska | 68502 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23549864 | Derived | Upreti VV, Keung CF, Boulton DW, Chang M, Li L, Tang A, Hsiang BC, Quamina-Edghill D, Frevert EU, Lacreta FP. Bioequivalence of saxagliptin/metformin immediate release (IR) fixed-dose combination tablets and single-component saxagliptin and metformin IR tablets in healthy adult subjects. Clin Drug Investig. 2013 May;33(5):365-74. doi: 10.1007/s40261-013-0075-z. |
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58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).
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| ID | Title | Description |
|---|---|---|
| FG000 | All Treated Participants | Participants were assigned to 1 of 4 treatment sequences (A-D-B-C, B-A-C-D, C-B-D-A, D-C-A-B). Treatment A=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fasted; Treatment B=fixed-dose combination (FDC) tablet of 2.5-mg saxagliptin/1000-mg metformin immediate release (IR), fasted; Treatment C=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fed; Treatment D=FDC tablet of 2.5-mg saxagliptin/1000-mg metformin IR, fed. The washout between each dose was at least 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Enrolled and Treated Participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng*h/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted | Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| EYE DISCHARGE | Eye disorders | MedDRA 12 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boaz Hirschberg | AstraZeneca Pharmaceuticals | ClinicalTrialTransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C502994 | saxagliptin |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Metformin IR (glucophage) | Drug | Tablets, Oral, 1000 mg, Once Daily, 1 week |
|
|
| Saxagliptin + Metformin IR (FDC) | Drug | Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week |
|
|
Single-dose PK parameters of metformin were derived from plasma concentration versus time data. |
| pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Metformin PK Parameter AUC(0-T) | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Metformin PK Parameter Cmax | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Metformin PK Parameter T-HALF | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Metformin PK Parameter Tmax | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. |
| pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| BMS-510849 PK Parameter Cmax | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| BMS-510849 PK Parameter T-Half | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| BMS-510849 PK Parameter T-Max | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
| Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study. |
| AEs of Special Interest | See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class [SOC]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity. | AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). |
| Number of Participants With Marked Laboratory Abnormalities (MA) | Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10^3 c/uL; absolute neutrophils/bands LN, 1.500x10^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L. | Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. |
| Number of Participants With Marked Urinalysis Abnormalities | Protein, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Glucose, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Blood, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). White Blood Cell (WBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). Red Blood Cell (RBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.) | Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. |
| Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | 12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs. | At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation |
| Did not Return for the Clinic Visit |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
|
| weight | Mean | Standard Deviation | kg |
|
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions |
| OG002 | 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal |
| OG003 | FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal |
|
|
|
| Secondary | BMS-510849 PK Parameter AUC(INF) | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng*h/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Primary | Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T]) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng*h/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
|
| Primary | Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
|
| Primary | Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Mean | Standard Deviation | hours | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Primary | Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax) | Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Median | Full Range | hours | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Primary | Metformin PK Parameter AUC(INF) | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng*h/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
|
| Primary | Metformin PK Parameter AUC(0-T) | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng*h/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
|
| Primary | Metformin PK Parameter Cmax | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
|
| Primary | Metformin PK Parameter T-HALF | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Mean | Standard Deviation | hours | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Primary | Metformin PK Parameter Tmax | Single-dose PK parameters of metformin were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Median | Full Range | hours | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Secondary | BMS-510849 PK Parameter AUC(0-T) | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng*h/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Secondary | BMS-510849 PK Parameter Cmax | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Geometric Mean | Full Range | ng/mL | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Secondary | BMS-510849 PK Parameter T-Half | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective plasma concentration versus time data. | Treated participants with PK measures | Posted | Mean | Standard Deviation | hours | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Secondary | BMS-510849 PK Parameter T-Max | Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data. | Treated participants with PK measures | Posted | Median | Full Range | hours | pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period |
|
|
|
| Secondary | Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs | An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | All treated participants | Posted | Number | participants | AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study. |
|
|
|
| Secondary | AEs of Special Interest | See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class [SOC]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity. | All treated participants | Posted | Number | participants | AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). |
|
|
|
| Secondary | Number of Participants With Marked Laboratory Abnormalities (MA) | Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10^3 c/uL; absolute neutrophils/bands LN, 1.500x10^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L. | Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure. | Posted | Number | participants | Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. |
|
|
|
| Secondary | Number of Participants With Marked Urinalysis Abnormalities | Protein, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Glucose, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Blood, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). White Blood Cell (WBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). Red Blood Cell (RBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.) | Number of Participants Analyzed=treated participants; n=number of participants evaluated for this measure (among the 6 participants who had the urinary WBC and RBC test, there are only 2 had a pre-study evaluation, and were therefore evaluable for these measures. | Posted | Number | participants | Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. |
|
|
|
| Secondary | Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities | 12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs. | Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure. | Posted | Number | participants | At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation |
|
|
|
| 0 |
| 19 |
| 3 |
| 19 |
| EG001 | FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions | 0 | 19 | 2 | 19 |
| EG002 | 2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed | Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal. | 0 | 21 | 2 | 21 |
| EG003 | FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed | Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal. | 0 | 24 | 3 | 24 |
| EG004 | Not Dosed | 58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons). | 0 | 34 | 0 | 34 |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 12 | Systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA 12 | Systematic Assessment |
|
| BLOOD LACTATE DEHYDROGENASE INCREASED | Investigations | MedDRA 12 | Systematic Assessment |
|
| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA 12 | Systematic Assessment |
|
| PALPITATIONS | Cardiac disorders | MedDRA 12 | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA 12 | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | MedDRA 12 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| DYSPEPSIA | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| FLATULENCE | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 12 | Systematic Assessment |
|
| EAR PAIN | Ear and labyrinth disorders | MedDRA 12 | Systematic Assessment |
|
| EAR DISCOMFORT | Ear and labyrinth disorders | MedDRA 12 | Systematic Assessment |
|
| MENSTRUATION DELAYED | Reproductive system and breast disorders | MedDRA 12 | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 12 | Systematic Assessment |
|
| PAIN IN JAW | Musculoskeletal and connective tissue disorders | MedDRA 12 | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 12 | Systematic Assessment |
|
| RHINORRHOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 12 | Systematic Assessment |
|
| SINUS CONGESTION | Respiratory, thoracic and mediastinal disorders | MedDRA 12 | Systematic Assessment |
|
| THROAT IRRITATION | Respiratory, thoracic and mediastinal disorders | MedDRA 12 | Systematic Assessment |
|
| OROPHARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA 12 | Systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| D004700 | Endocrine System Diseases |
| To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect. | adjusted geometric mean | 0.992 | 2-Sided | 90 | 0.962 | 1.022 | Yes | Non-Inferiority or Equivalence | Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity. |
| To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect. | adjusted geometric mean | 0.987 | 2-Sided | 90 | 0.900 | 1.083 | Yes | Non-Inferiority or Equivalence | Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity. |
| To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect. | adjusted geometric mean | 0.966 | 90 | 0.915 | 1.020 | Yes | Non-Inferiority or Equivalence | Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity. |
| To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect. | adjusted geometric mean | 0.974 | 90 | 0.920 | 1.032 | Yes | Non-Inferiority or Equivalence | Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity. |
| To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect. | adjusted geometric mean | 0.964 | 2-Sided | 90 | 0.891 | 1.042 | Yes | Non-Inferiority or Equivalence | Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity. |
| SAEs |
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| AEs |
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| Discontinuations dues to AEs |
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| Abs. Neutrophils/Bands-Low (<=lower LN [LLN]) |
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| Aspartate Aminotransferase - High (>1.25 * ULN) |
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| Alanine Aminotransferase - High (>1.25 * ULN) |
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| Blood Urea Nitrogen - High (1.1 * ULN) |
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| Creatine Kinase - High (>1.5 ULN) |
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| Lactate Dehydrogenase - High (>1.25 ULN) |
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| Glucose, Urine (n=19, 19, 20, 21) |
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| Blood, Urine (n=19, 19, 20, 21) |
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| White Blood Cells, Urine (n=2, 2, 2, 2) |
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| Red Blood Cells, Urine (n=2, 2, 2, 2) |
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| Vital Sign Abnormalities |
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| Physical Finding Abnormalities |
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